CN110739199B - Method and system for detecting ion spatial distribution - Google Patents

Abstract

An ion detection system comprising: a microchannel plate stack comprising a front face and a rear face, the stack being arranged to receive an ion flux from the exit aperture of the quadrupole rod at the front face and to emit an electron flux in response to the received ion flux at the rear face; a scintillator having a front surface and a back surface and arranged to receive a flux of electrons at the front surface and to emit a flux of photons at the back surface in response to the received flux of electrons; a light imager configured to receive the flux of photons; a power source; first, second and third electrodes connected to a power supply and disposed on the front, rear and first surfaces, respectively, wherein the scintillator includes a single crystal plate of a phosphorescent material.

Description

Method and system for detecting ion spatial distribution

Technical Field

The present invention relates to the field of mass spectrometry. More particularly, the present invention relates to a mass spectrometer detector system and method in which ions exiting a quadrupole mass analyzer are converted into a quantity of electrons, and the electrons are converted into a quantity of photons which are focused onto an image plane and imaged by a light imager.

Background

Quadrupole mass filters are commonly used as components of tertiary mass spectrometry systems. As a non-limiting example, fig. 1A schematically illustrates a triple quadrupole rod system, as indicated by reference numeral 1. The operation of the mass spectrometer 1 may be controlled and the data 68 may be acquired by one or more of various circuit control and data systems (not shown) of known type, which may be implemented as any one or combination of general or special purpose processors, such as Field Programmable Gate Arrays (FPGAs), firmware, software, to provide instrument control and data analysis for the mass spectrometer and/or associated instruments. A sample containing one or more target analytes may be ionized by an ion source 52 operating at atmospheric or sub-atmospheric or near sub-atmospheric pressure. The resulting ions are directed through predetermined ion optics, which may often include tube lenses, splitters (skimmers), ion funnels 51 and multipoles (e.g., reference characters 53 and 54), to be forced through a series of progressively reduced pressure chambers, such as chambers 2, 3 in fig. 4, which are operable to direct and focus these ions to provide good transport efficiency. Each chamber communicates with a respective port 80 (represented by an arrow in fig. 1A), the ports 80 being connected to a set of vacuum pumps (differential pumping, not shown) to maintain the pressure at a desired value.

The example mass spectrometer system 1 of FIG. 1A is diagrammatically shown to include a tertiary configuration 64 within the high vacuum chamber 5 having portions labeled Q1, Q2, and Q3 electrically connected to respective power sources (not shown). The Q1, Q2, and Q3 stages may operate as a first quadrupole mass filter, a fragmentation unit, and a second quadrupole mass filter, respectively. The ions are analyzed or filtered in a first stage, fragmented in a second stage, and/or analyzed or filtered in a final stage, and then passed to a detector 66. Such detectors are advantageously placed at the exit of a quadrupolar channel (e.g., Q3 of fig. 1A) to provide ion abundance information, which can be processed into a rich mass spectrum (data) 68 showing the change in ion abundance relative to the m/z ratio. With the recent development of imaging ion detectors for detecting ions emerging from quadrupole mass filters (see detailed discussion below), three-dimensional information (e.g., two spatial dimensions and one temporal dimension) can be obtained that maintains high mass resolving power without significant signal strength degradation.

During conventional operation of a multipole mass filter (e.g., quadrupole mass filter Q3 shown in fig. 1A), to generate a mass spectrum, a detector (e.g., detector 66 of fig. 1A) is used to measure the amount of ions that pass completely through the mass filter as a function of time during application of superimposed oscillating Radio Frequency (RF) and non-oscillating (DC) electric fields. Thus, at any point in time, the detector receives only those ions that have an m/z ratio within the mass filter pass band at that time-that is, only those ions that have a stable trajectory within the multipole at the particular RF and DC voltages applied to the quadrupole rods at that time. This conventional operation creates a compromise between instrument resolution and sensitivity. High mass resolution can be achieved but only if the DC/RF ratio makes the filter pass-band very narrow, so that most ions produce unstable trajectories within the mass filter and rarely pass the detector. In this case, the scan must be performed relatively slowly in order to detect a sufficient number of ions at each m/z data point. Conversely, high sensitivity or high speed can also be achieved during conventional operation, but only by widening the passband, resulting in a reduction in m/z resolution.

U.S. patent 8,389,929, assigned to the assignee of the present invention and incorporated herein by reference in its entirety, teaches a quadrupole mass filtering method and system that distinguishes between ion species by recording the position at which ions strike a position sensitive detector as a function of applied RF and DC fields, even when both are stable at the same time. When recording the time of arrival and position, the resulting data can be viewed as a series of ion images. Each observed ion image is essentially a superposition of component images corresponding to each distinct m/z value that leaves the quadrupole at a given time. This patent also teaches a method for predicting an arbitrary ion image as a function of m/z and the application field. Thus, each individual component image may be extracted from a series of observed ion images by a mathematical deconvolution or decomposition process, as further discussed in the aforementioned patents. The mass-to-charge ratio and abundance of each species must come directly from deconvolution or decomposition. Thus, high mass resolving power can be achieved under a variety of operating conditions, a property not normally associated with quadrupole mass spectrometers.

The inventors of us patent 8,389,929 have recognized that even when two ions are stable (i.e. have stable trajectories) simultaneously within a mass filter, ions of different m/z ratios exiting a quadrupole mass filter can be distinguished by recording the position at which the ions impact a position sensitive detector as a function of the applied RF and DC fields. The inventors of us patent 8,389,929 have recognized that such operation is advantageous because the scanning of the device provided by the ramped RF and DC voltages naturally changes the spatial characteristics over time when the quadrupole is operated in, for example, mass filter mode, as observed at the quadrupole exit. In particular, ions manipulated by quadrupole rods are induced to perform complex two-dimensional oscillatory motions on the detector cross-section as they are scanned through a stable region of ions. All ion species of the respective m/z ratios represent exactly the same motion over the same range of values of the Mathieu parameters "a" and "q" (see fig. 13), but at different respective RF and DC voltages and at different respective times. Ion motion (i.e., for ion clouds of the same m/z but with various initial displacements and velocities) can be characterized by the variation in a and q that affects the position and shape cloud of ions leaving the quadrupole rods over time. For two masses that are nearly identical, the order of their respective oscillatory motions is substantially the same and can be roughly correlated by time shifting.

The teaching of the above-mentioned us patent 8,389,929 exploits the varying spatial characteristics by collecting spatially dispersed ions of different m/z, even if they leave the quadrupole rods substantially simultaneously. Fig. 1B shows a simulated recorded image of a particular pattern at a particular time. Example images may be collected by a fast detector (i.e., a detector capable of fast sampling over 10 or more RF cycles, more often to RF cycles or with sub-RF cycle specificity, which may be averaged over multiple RF cycles) positioned to acquire the location and time of ion departure to differentiate details. The movement of the ions can be referred to a conventional Mathieu diagram (FIG. 13). During the mass scan, the (q, a) position of any ion is described by motion along scan line 411. During scanning, the (q, a) position of the ion first approaches (point 413), then enters (point 412), then passes (point 415) and finally leaves the "X and Y stable" part of the Mathieu diagram (point 414). During this time, the y-component of the ion trajectory changes from "unstable" to "critically stable" at the instability boundary (point 412) and then becomes increasingly "stable" after ( points 415, 414, and 416). At the same time, the x-component of the ion trajectory changes qualitatively in the opposite sense. Observing the ion image formed in the exit cross-section progresses in time, the ion cloud is elongated and undergoes wild oscillations (referred to herein as "vertical" oscillations) along the y-axis, carrying it beyond the top and bottom of the collected image. Gradually, the exit cloud contracts, and when the (q, a) scan line is in a stable region of the ion of interest, the amplitude of the y-component oscillation decreases. If the cloud is sufficiently compact when entering the quadrupole rods, the entire cloud remains in the image during a complete oscillation period with the ions fully within the stable region, i.e. 100% transmission efficiency.

Fig. 1B graphically illustrates such a result. In particular, a vertical ion cloud, as enclosed by the ellipse 6 illustration shown in fig. 1B, corresponds to heavier ions entering the steady field of the quadrupole rods and thus oscillating at an amplitude that brings such heavy ions close to the represented y-quadrupole. The cluster of ions graphically surrounded by the ellipse 8 shown in fig. 1B corresponds to the lighter ions leaving the steady field of the quadrupole rods and thus oscillating these ions at an amplitude such that the lighter ions approach the represented x-quadrupole. There are additional clusters of ions within the image (shown in fig. 1B but not particularly highlighted) that have been collected at the same time horizon but have different exit patterns due to differences in their Mathieu a and q parameters.

Fig. 1C shows one example of an imaging ion detector system, generally designated by the reference numeral 20, as described in the aforementioned U.S. patent 8,389,929. As shown in fig. 1C, incident ions I (schematically illustrated by the drawing arrows) are received by the assembly 102 of microchannel plates (MCPs) 13a, 13b, which have a beam cross-section of, for example, about 1mm or less, that changes to the inscribed radius of the quadrupoles as they exit from the ion occupied volume between the quadrupole rods 101. Such an assembly may include a pair of MCPs (Chevron or V-stack) or three MCPs (Z-stack) comprising adjacent to each other, each individual plate having sufficient gain and resolution to enable operation at appropriate bandwidth requirements (e.g., at about 1MHz to about 100MHz), the combination of plates producing up to about 10 in response to each incident ion⁷And (4) electrons.

To illustrate operability, the first surface of the MCP assembly 102 may float to 10kV (i.e., +10kV when configured as negative ions and-10 kV when configured to receive positive ions) and the second surface floats to +12kV and-8 kV, respectively, as shown in FIG. 1C. This plate bias provides a voltage gradient of 2kV to provide a gain with a resulting output of 8 to 12kV with respect to ground. All high voltage parts are at about 10^-5Mbar (10)^-3Handkerchief) and 10^-6Mbar (10)^-4Pascal) under vacuum.

The exemplary bias arrangement of fig. 1C thus enables ions I received from, for example, the exit of a quadrupole, as described above, to be impacted to induce electrons in the front surface of first MCP 13a in the case of positive ions, which are then directed to travel along the various channels of first MCP 13a, accelerated by the applied voltages. As known to those skilled in the art, since each channel of the MCP functions as an independent electron multiplier, input ions I received on the channel walls produce an emission of secondary electrons (denoted as e)^–). These electrons are then accelerated by the potential gradient across the ends of each individual MCP 13a, 13b of MCP stack 102 and strike the inner surfaces of the channels, causing more electron emissions to be released from the output of MCP stack 102. This process is essentially capable of preserving the pattern (image) of particles incident on the front surface of the MCP. When operating in the negative ion mode, the negative ions are initially converted to small positive ions, which then cause a similar cascade of electrons, as is well known in the art.

The offset arrangement of the detector system 20 (fig. 1C) also causes the electrons multiplied by the MCP stack 102 to be further accelerated so as to strike an optical component, e.g., a phosphor-coated fiber plate 15, disposed behind the MCP stack 102. This arrangement converts the signal electrons into a plurality of resulting photons (denoted as p) proportional to the amount of received electrons. Alternatively, the optical components (e.g., an aluminized phosphor screen) may be provided with a biasing arrangement (not shown) such that the resulting electron cloud from the MCP stack 102 may be attracted to the phosphor screen across the gap by a high voltage, with the kinetic energy of the electrons being released as light. The initial assembly was configured to convert positive or negative ion images emanating from the quadrupole rod exit into photon images suitable for acquisition by subsequent photon imaging techniques.

Photons p emitted by the phosphor coated fiber optic plate or aluminized phosphor screen 15 are captured and then converted to electrons, which are then converted to digital signals by a two-dimensional camera assembly 25 (fig. 1C). In the arrangement shown, a plate such as a photo channel plate 10 assembly (anode output shown offset with respect to ground) can convert each incoming photon p back into a photo-electron. Each timeThe individual photons generate a secondary electron cloud 11 (denoted e) on the back of the photosensitive channel plate 10^-) Which spreads and impinges upon an array of sense anodes 12 as an arrangement such as, but not limited to, a two-dimensional array of resistive structures, two-dimensional delay line wedge and strip designs, and commercial or custom delay line anode readout. As part of the design, the photosensitive channel plate 10 and anode 12 are located in a sealed vacuum enclosure (not shown).

Each anode of the two-dimensional camera 25 shown in fig. 1C is coupled to a separate amplifier 14 and an additional analog-to-digital converter (ADC)18, as is known in the art. This independent amplification can be done, for example, by a differential transimpedance amplifier or Avalanche Photodiode (APD) to improve the signal-to-noise ratio and convert the detected current into a voltage. The signals from the amplifier 14 and ADC 18 and/or charge integrator (not shown) may ultimately be directed through, for example, a serial LVDS (low voltage differential signaling) high-speed digital interface 21 to a Field Programmable Gate Array (FPGA)22, which is a component designed for low power consumption and high noise immunity at the desired data rate. When electrically coupled to a computer or other data processing device 26, the FPGA 21 can operate as a dedicated hardware accelerator for the required computationally intensive tasks.

Fig. 2 schematically depicts an imaging ion detection system as described in U.S. patent 9,355,828, the entire contents of which are incorporated herein by reference. The imaging ion detection system is shown generally in fig. 2 as detector system 100. Ions I exiting from the ion footprint between the quadrupole rods 101 are converted to electrons and the electron current is amplified by the microchannel plate assembly or stack 102 comprising one or more microchannel plates, as previously described with reference to fig. 1C. The photons are preferably generated within the system 100 using a substrate 109 that includes a single or unitary component (e.g., a glass, mica, or plastic plate) coated with a transparent material (e.g., indium tin oxide), which includes the bias electrode 106 and is further coated with a phosphor material that includes a phosphor screen 107. A phosphor coated plate comprising a bundle of fibers, such as the plate 15 employed in the system 20 shown in fig. 1C, may alternatively be used as the substrate 109. Voltage V₁And V₂Is applied to electrodes at opposite ends of the MCP stack 102 so as toAttracting ions I to the stack and accelerating the generated electrons (denoted e)^–) By stacking. Voltage V₃Is applied to the transparent electrode 106 to attract electrons to the phosphor screen 107 where photons (denoted P) are generated.

A set of components 27 shown on the right hand side of the substrate 109 in fig. 2 is used in place of the two-dimensional camera 25 shown in fig. 1C. The alternate components include two separate linear (one-dimensional or "1-D") photodetector arrays 132a, 132b and associated optics. In operation, the phosphor screen 107 "shines" emittingly at a spatially non-uniform intensity as it is subjected to electrons e generated as a result of ions I striking the microchannel plate assembly or stack 102^–The influence of (c). This spatially non-uniform emission pattern at any time corresponds to the spatial distribution of the number of ions emitted from between the quadrupole rods 101 at that time. The lens 112 and cylindrical lens 121a are used to transfer an image of the lumiphoric phosphor screen onto a first linear photodetector array (PDA)132 a. Likewise, lens 112 and cylindrical lens 121b are used to transfer a replicated image of the lumiphoric screen onto a second linear photodetector array 132 b. The axis of the cylindrical lens 121b is oriented substantially perpendicular to the axis of the cylindrical lens 121 a. Similarly, the individual photosensitive elements of the photodetector array 132b are aligned along a line that is substantially perpendicular to a second line along which the individual photosensitive elements of the linear photodetector array 132a are aligned. The illustrated shape difference between the first and second cylindrical lenses 121a, 121b is taken to indicate that the second cylindrical lens includes a rotated orientation such that its axis is orthogonal to the first cylindrical lens.

Light, including photons generated by the phosphor screen 107 and passing through the substrate 109, is collected and partially collimated into a beam by the light collection lens 112. The partially collimated beam is then split into two beam portions by the beam splitter 116 along two respective paths. A first such path-traversed by the first beam portion-is indicated in fig. 2 by arrow 117, and a second such path-traversed by the second beam portion-is indicated by arrow 118. These beam portions thus transmit two copies of the image information. Each of these beam portions may then comprise about half the intensity of the original light source. Alternatively, the beam splitter 116 may be configured such that the ratio between the intensities of the transmitted and reflected beam portions is not one-to-one (1: 1), e.g., nine-to-one (9: 1), four-to-one (4: 1), one-to-four (1: 4), one-to-nine (1: 9), etc. Such beamsplitters are commercially available as off-the-shelf inventory items or can be customized to virtually any desired transmission reflectance. For example, a method in which the transmission reflectance is not 1: 1 to pass a greater proportion of the beam intensity to a less sensitive detector or a smaller proportion to a detector that may be susceptible to saturation.

Each of the two beam portions is focused by a respective one of the cylindrical lenses 121a, 121b to project a respective one-dimensional image of the phosphor screen onto a respective one of the linear photodetector arrays 132a, 132 b. Optionally, a reflecting means 123, comprising e.g. a plane mirror or a prism, may be employed in one beam path to make the two beams parallel. The deflection of one of the beams by the reflecting device 123 may be used to reduce the size of the system 100 or may be helpful in mechanically mounting the two linear photodetector arrays 132a, 132b to a common circuit board and drive electronics.

According to the configuration shown in fig. 2, the beam portion that traverses the path shown by arrow 117 is compressed in the x-dimension (see cartesian axes on the left side of fig. 2) so as to be focused into a line (i.e., a line parallel to the y-dimension, perpendicular to the plane of the drawing of fig. 2) that coincides with the position of the first linear photodetector array 132 a. Similarly, the portion of the beam that passes through the path shown by arrow 118 is compressed in the y-dimension to focus to a line parallel to the x-dimension and coincident with the position of the second linear photodetector array 132 b. The photosensitive areas of the linear photodetector arrays 132a, 132b are disposed at the focal points of the cylindrical lenses 121a, 121b such that each beam portion is focused as a line on the photosensitive area of the respective linear photodetector array 132a, 132 b. The first and second linear photodetector arrays 132a, 132b may include, but are not limited to, two line cameras. The first and second linear photodetector arrays 132a, 132b may be substantially identical to each other. However, the first and second linear photodetector arrays 132a, 132b are shown differently in fig. 2 to indicate that the direction of the second linear photodetector array 132b is rotated so as to be orthogonal to the first linear photodetector array 132 b.

Fig. 3 is a schematic diagram of the light receiving face of a generally linear photodetector array 132. The array includes a plurality of individual, independent photosensitive elements 133, which may be referred to as "pixels". In the system 100 shown in fig. 2 (and in other system embodiments taught herein), an example of the array 132 may be optically connected to a cylindrical lens 120a, 120b or a line-focus compound lens, where a plurality of pixels arranged linearly are oriented so as to coincide with a line focus produced by the cylindrical lens or the compound lens.

As shown in fig. 2, each linear photodetector array maintains the image variation along the dimension parallel to the array and sums (or "partitions") the image information orthogonal to the array. Because two mutually orthogonal arrays are employed, image variations parallel to the x-direction and y-direction (as defined above for a quadrupole device) are preserved. Partitioning information is a very useful method of data compression without losing too much information. The system configuration depicted in fig. 2 includes optics to enable the use of two separate simpler photodetector arrays, such as a line camera, to provide the same quadrature information as the two-dimensional camera 25 (fig. 1C) previously described.

Fig. 4A is a simplified depiction of a portion of a known time and position imaging ion detector system for a mass spectrometer. As described above, the ion I-stream or flux emitted from the exit aperture 108 of the quadrupole rods 101 comprising four parallel rods is intercepted by the stack 102 of microchannel plates 13a, 13 b. In response to the impact of the ions, electrons e^–Is ejected from the MCP stack. The flow or flux of electrons retains spatial information about the original flux density of the intercepted ions at each location on the MCP stack. These electrons are intercepted by the scintillator substrate 109 coated with the phosphor material 107. Typically, the phosphorescent material is a sintered powder of, for example, Ce: YAG (cerium doped yttrium aluminum garnet). At a bias voltage V supplied by a high voltage power supply 31₁Is forced from the quadrupole rods 101 towards the MCP stack. At a bias voltage V₂And V₃Influence of (2)The down-emitted electrons are pushed from the first MCP 13a to the second MCP 13b, and then the scintillator plate 109, where the latter may be provided to the thin film electrode coating 104 on the scintillator. Applied voltage V₁And V₂A voltage gradient of 2kv is provided to provide gain between the plates. All high voltage sections are in a vacuum state. The electronic controller 33, which may be a programmed computer or other integrated circuit programmed by firmware, controls the application of voltages to the MCP and the electrodes 104, and also controls the application of Radio Frequency (RF) and other voltages to the rod electrodes of the quadrupole 101.

The first two components of the detection system (MCP and scintillator material) often age unevenly in a short time due to the influence of a high intensity ion beam that can be under vacuum (e.g., 10 f) at one or more quadrupole rods 101^-5To 10^-6Torr) is focused at a particular point on the MCP and scintillator surfaces during the RF cycle. For example, fig. 4B shows a time series of ion images of a single isotope polytyrosine-1, which is captured by a detector system having the components shown in fig. 4A. The abscissa in fig. 4B represents time and the ordinate represents the displacement of the image along the y-axis (along the contour 202 at the top of the figure) and along the x-axis (along the contour 204 at the bottom). The signal intensity is represented by the darkness of the shading. The apparent asymmetric ion trajectories observed in the y-dimension at position 205 are due in part to the non-uniform gain distribution of the detection region. The non-uniform gain across portions of the MCP and/or phosphor surface due to rapid ion aging imposes an asymmetric wave profile in the time series of images along the y-dimension, as shown by the envelope 209 in fig. 4C.

Indeed, to achieve detection of single ion events, high gain/potential on MCP and phosphor is typically required, which is a standard requirement for commercial quadrupole mass spectrometry instruments. The most severe aging was found to occur at the locations on the beam-focused MCP and the scintillator. Long-term studies of MCP and phosphor show significant gain variation at specific points on the plate surfaces during one week of normal quadrupole mass spectrometer operation. Fig. 4D is a schematic illustration of an impact region 211 of ions or electrons on a surface of a microchannel plate or scintillator of an imaging ion detector system, such as the system shown in fig. 1C and 2. In this discussion, the term "transducer" is used to refer to a microchannel plate or scintillator plate, and is identified in the description of the figures as transducer 215. In other words, each figure in which the transducer 215 is shown may represent either or both of two different objects — a first object in which the transducer 215 is a microchannel plate, and possibly a second object in which the transducer 215 is a scintillator plate. In case the transducer is a microchannel plate (MCP), the charged particles are ions; in case the transducer is a scintillator plate, the charged particles are electrons. In either case, the center of the transducer face is depicted at 213.

The ion impact region 211 of the transducer 215 includes two sub-regions, denoted as sub-region 219a and sub-region 219 b. The sub-region 219a is a portion of the region 211 in which the charged particles carry sufficient energy to cause a rapid decrease in the transducer response over a period of time after the transducer is placed into use. The sub-zone 219b, which is the remaining part of the area of the impact region 211, is a part of the transducer surface inside which measurable amounts of charged particles hit the transducer surface but inside which the total energy flux is not so large as to cause a significant change of the response of a new transducer within a short period of time (e.g. several weeks). Although depicted with clear demarcations in fig. 4D, the outer boundary of the region 211 and the boundary between the sub-region 219a and the sub-region 219b are in fact graduated. Moreover, the relative sizes of the transducer 215 and the regions 219a-219b are schematic and not necessarily drawn to scale.

When the transducer 215 is properly aligned near the exit aperture of the rods X1, X2, Y1, Y2 (see fig. 5) of the quadrupole mass analyzer, the projection of the transducer center 213 and the quadrupole center longitudinal axis 210 coincide onto the surface. Because the central longitudinal axis is the location of the pseudopotential well within the quadrupole rod, all ions with a stable trajectory oscillate about this axis and pass through a narrow region about this axis multiple times as they pass through the quadrupole rod. Thus, the sub-regions 219a of the MCP receive the greatest amount of ions over time, and the corresponding sub-regions 219a of the scintillator plate receive the greatest amount of electrons over time, because the large potential difference guides ions along the central longitudinal axis 210. Thus, sub-region 219a is referred to herein as the ion focus region and is the region of greatest signal intensity in the ion image produced by an imaging system of the type shown in fig. 1C and 2. Unfortunately, image details originating from the subregion 219a may be biased due to transducer aging over time, because the subregion 219a has the greatest probability of being affected by ions or electrons, regardless of the m/z value. In contrast, the signal intensity originating from sub-region 219B is lower than the signal originating from sub-region 219B, but still shows a greater variability for m/z (see FIG. 1B). Mathematical analysis of the image time series requires information from both sub-regions 219a, 219b in order to fully resolve the component signals corresponding to different respective ion m/z values.

Data processing of imaging quadrupole mass spectrometer systems such as those shown in figures 1C and 2 includes a deconvolution step that decomposes complex overlapping data resulting from multiple emerging ion species into separate component images, each of which is associated with one of these species. The data processing also includes identifying temporal variations of such component images. Such data processing steps that are sensitive to changes in the spatial pattern of emerging ions require consistent measurements from the detection system. If the sensitivity of the detection system should deviate from its condition during the most recent calibration, a system recalibration is required to prevent data processing performance degradation or complete failure. As shown by long life experiments, a weekly calibration schedule may be unacceptable to most users. There is therefore a need in the art to extend the effective period of detector calibration in a quadrupole mass spectrometer system that detects spatial patterns of ions.

Disclosure of Invention

In view of the need for mass spectrometry technology, the inventors devised apparatus and methods to extend the duration of time that a single calibration can be successfully used in mass analysis with a time and position imaging mass spectrometer. The apparatus according to the present teachings may include one or both of: (a) a stack of three or more microchannel plates (MCPs) and (b) a scintillator plate, e.g. Ce: GAGG (cerium-doped gadolinium aluminium gallium garnet), in the form of a sintered powder or a single crystal. The multi-plate MCP stack includes three or more individual plates that disperse the potential gradient so that the aging of each plate is more gradual over time during operation of the mass spectrometer than operation using fewer than three plates. For high MCP gain operation, the final plate receiving most electrons may require a pre-aging process to stabilize the gain variation. It was found that using Ce: GAGG as the phosphorescent material yields higher photon gain than conventional Ce: YAG while also exhibiting higher aging resistance.

The present teachings also include various methods of operating a time and position imaging mass spectrometer that reduce the rate of aging of MCPs and scintillator packs (both referred to herein as "transducers"). In a first group of such methods, the MCP stack and/or the scintillator physically migrate during operation of the mass spectrometer such that the ion beam in the case of the MCP stack or the electron beam in the case of the scintillator migrates over the surface of the respective transducer, thereby reducing the rate at which any point on the scintillator surface is exposed to the incident charged particle beam. The movement of the transducer may be continuous or stepwise and is preferably effected by at least two mechanical actuators physically connected to the carriage on which the transducer is mounted. Preferably, the first and second actuators effect movement in mutually orthogonal directions, for example along the x-axis and along the y-axis, the axes being defined relative to the quadrupole axis. The movement may be parallel to either axis or may be non-parallel to both axes. Preferably, the movement of the transducer conforms to a predetermined movement pattern.

According to a second set of methods of the present teachings, the MCP stack and/or the scintillator remain stationary with respect to the quadrupole rods while the ion beam within the quadrupole rods is caused to migrate around the central longitudinal axis by controlled application of separate, independent, unequal DC potentials to at least two rods that are radially opposite to each other with respect to the central longitudinal axis of the quadrupole rods. This method may be performed to cause the ion beam to gradually migrate around the surface of the MCP, similar to the effect of the physical motion of the transducer. Thereby simultaneously causing the respective electrons to migrate around the surface of the associated scintillator plate. An unbalanced voltage can be controllably applied across the pair of x-rods and across the pair of y-rods such that the particle beam migrates according to a predetermined pattern relative to the x-and y-axes. The ion beam migration may be continuous or stepwise.

The above-described method in which the ion beam or transducer is repositioned or translated ensures that the ion beam or electron beam does not remain stationary at any one particular location of the associated transducer for a long period of time, thereby reducing the rate of response degradation at the transducer surface and allowing the imaging mass spectrometer ion detector to operate for a long period of time between calibrations. These methods may be used in conjunction with known time and position imaging mass spectrometer detector systems, such as one of the detector systems shown in fig. 1C and 2 or other such systems described in U.S. patent 8,389,929, the entire contents of which are incorporated herein by reference. Alternatively, these methods may be used in conjunction with a time and position imaging mass spectrometer detector system, which is modified with one or both of the modifications shown in FIG. 6.

According to another set of methods of the present teachings, a time and position imaging mass spectrometer is operated such that a supplemental low frequency Alternating Current (AC) voltage waveform is applied to the rods of a quadrupole. During a mass analysis experiment, the frequency (or component frequency) of the AC wave is selected to match the existing frequency or frequencies of the target mass-to-charge ratio. The low frequency AC waveform may be phase synchronized with the sweeping RF waveform and may be applied to two pairs of rods having opposite phases or only to one pair of opposing rods. As is well known in the art of mass spectrometry, such resonance excitation imparts additional energy to ions containing the target m/z value, thereby increasing the oscillation amplitude of such excited ions. The amplitude of the AC waveform is selected so that ions having the target m/z value have a greater likelihood of being detected away from (rather than within) the ion focusing region, and so that the target ions are not ejected laterally from the interior of the quadrupole. The increased amplitude of oscillation of these ions results in a reduced ion flux at the center of the transducer, thereby reducing the rate of aging of the transducer within the mass spectrometer.

According to another set of methods of the present teachings, the transducer (MCP or scintillator) may be "pre-aged" before being put into use within a time and position imaging mass spectrometer system. Pre-ageing may be achieved by impinging an electron beam on all or part of the surface of the transducer, driven by a potential difference between the emitter and the transducer. Once placed into service within a mass spectrometer, the pre-aged portion of the transducer will be less susceptible to additional degradation of the transducer response than the non-aged transducer or the non-aged portion of the single transducer. In this way, the duration of the effectiveness of the calibration of the mass spectrometer detector can be extended once the transducer is put into use, as the effectiveness of such calibration depends on the constancy of the detector response.

The pre-ageing of the transducer may be uniform over the surface of the transducer, or alternatively, according to a predetermined pattern. In some methods of the present teachings, an aging pattern may be imposed on the transducer by selectively and controllably scanning or raster scanning the electron beam over all or part of the transducer. The scanning or raster scanning of the light beam may be achieved by physical movement of the transmitter and transducer relative to each other, or preferably, by controlled progressive electromagnetic deflection of the light beam according to a raster pattern. In other methods of the present teachings, the aging pattern can be applied to the transducer by passing an electron beam through a mask interposed between the electron emitter and the transducer, wherein the mask includes an encoded beam attenuation pattern that corresponds to or reflects a desired pre-aging pattern of the transducer. According to the method, the emitter, mask and transducer are preferably configured such that there is a one-to-one mapping between each point on the transducer on which the electron beam is incident and each point of the mask through which the beam passes. The degree of beam attenuation at each point on the mask is then reflected in the number of electrons allowed to strike a corresponding point on the transducer surface, in a reverse sense.

The final applied pattern includes different degrees of pre-aging at different parts of the transducer due to beam scanning or raster scanning or mask attenuation. In other words, the amount of pre-aging is a function of position on the transducer surface, which corresponds to or is a predetermined pattern of reflections. The predetermined pre-aging pattern may advantageously be selected to correspond to an expected ion flux pattern emerging from the quadrupole mass analyser. Preferably, the degree of aging is greatest at locations on the transducer surface where the greatest number of ions are expected to impinge. Thus, the aging pattern of the pre-aging transducer should be aligned in the mass spectrometer with the quadrupole rods positioned or rotated according to a predetermined alignment orientation such that the applied pre-aging pattern corresponds to the pattern of expected ion flux. Typically, the maximum number of ions is expected in the ion focusing region, which corresponds to the central region around the point corresponding to the extension of the central longitudinal axis of the quadrupole. With the transducers properly positioned and/or aligned and the ion flux pattern as expected, the portion of the ion beam containing the greatest ion flux will intercept the transducer surface at the most pre-aged region where the transducer is least susceptible to degradation of its response. At the same time, the more useful diagnostic portion of the ion beam, including the smaller beam flux, will intercept the transducer at the region of minimal or no pre-aging where the transducer is most sensitive to small changes in beam flux.

Pre-aged transducers specifically for use in time and position imaging mass spectrometers are considered devices in accordance with the present teachings. Likewise, a pre-aging method that is specific to a transducer used within a time and position imaging mass spectrometer is considered a method according to the present teachings. Similarly, the operation of a time and position imaging mass spectrometer using such a pre-aged transducer is considered a method according to the present teachings.

A time and position imaging mass spectrometer according to the present teachings can operate according to any method of the present teachings. For example, a time and position imaging mass spectrometer comprising any combination of: (a) an MCP comprising three or more plates; (b) a scintillator of the composition described herein; and (c) the one or more pre-aged scintillators can be operated in any combination of: (1) scintillator physical position migration; (2) ion beam position shifting; and (3) expanding the ion beam by resonant excitation of one or more selected target m/z values. All of these combinations are considered embodiments of the present invention.

Drawings

The above and various other aspects of the present invention will become further apparent from the following description, given by way of example only and with reference to the accompanying drawings, which are drawn to scale and in which:

FIG. 1A is a schematic example configuration of a three stage mass spectrometer system;

FIG. 1B is a simulated recording image of a plurality of different species of ions collected at the exit aperture of a quadrupole rod at a particular time;

FIG. 1C is a schematic diagram of a known time and position imaging ion detector system configured with a linear array of readout anodes;

FIG. 2 is a schematic diagram of a second known time and position imaging ion detector system employing two linear photodetector arrays;

FIG. 3 is a schematic diagram of a linear photodetector array;

FIG. 4A is a schematic diagram of a known imaging ion detector having a microchannel plate and a scintillator;

fig. 4B is a graphical depiction of the measured time variation of the detected ion current along the x and y directions of ions emitted from a quadrupole mass analyzer, as measured by an apparatus of the type shown in fig. 1C and 2;

FIG. 4C is an enlarged view of the variation in ion current detected in the y-direction at the exit aperture of a quadrupole mass analyzer, as measured by an apparatus comprising the assembly shown in FIG. 4A;

FIG. 4D is a schematic illustration of an impact region of ions or electrons on a surface of a microchannel plate or scintillator of an imaging ion detector system, further illustrating an accelerated aging region of the microchannel plate or scintillator;

FIG. 5 is a schematic diagram of a set of quadrupole rods of a mass analyzer, showing conventional application of a scanning Radio Frequency (RF) voltage (labeled RF0 and RF π) and a scanning Direct Current (DC) voltage (labeled DC1+ and DC1-) to the rods;

FIG. 6 is a schematic diagram of an imaging ion detector having a stack of microchannel plates and a scintillator according to the present teachings;

FIG. 7 is a schematic diagram of an exemplary pattern of charged particle beam migration across the surface of a microchannel plate during transport of ions onto the microchannel plate in a mass analysis process during which the microchannel plate is physically moved relative to the quadrupole, which pattern is also associated with the associated scintillator if the scintillator moves in concert with the motion of the microchannel plate;

FIG. 8A is a schematic diagram of a set of quadrupole rods of a mass analyzer indicating that a sweeping RF voltage (labeled RF0 and RF π), a first (sweeping) DC1 voltage (labeled DC1+ and DC1-), and a steering DC voltage (labeled DC2a through DC2b) are applied to the rods;

FIG. 8B is a schematic illustration of the steering pattern of the ion beam on the microchannel plates such that the aging of the microchannel plates and associated scintillators is evenly distributed over a certain area of each microchannel plate and scintillator;

FIG. 9A is a schematic diagram of a set of quadrupole rods of a mass analyzer, showing the application of a scanning RF voltage (labeled RF0 and RF π), a scanning DC voltage (labeled DC1+ and DC1-) and a supplemental oscillatory resonance excitation voltage (labeled AC0 and AC π) to the rods;

FIG. 9B is a schematic illustration of the contraction of the region of maximum charged particle flux incident on a microchannel plate or scintillator with a supplemental oscillatory resonance excitation voltage applied to the rods of a quadrupole mass analyzer to which the microchannel plate and scintillator are connected;

FIG. 10A is a schematic diagram of a method for pre-aging a microchannel plate or scintillator for use in a mass spectrometer ion imaging detector arrangement in accordance with the teachings of the present invention;

FIG. 10B is a schematic diagram of an alternative method for pre-aging a microchannel plate or scintillator for use in a mass spectrometer ion imaging detector arrangement in accordance with the teachings of the present invention;

FIG. 11A is a schematic illustration of a first exemplary pre-aging mode of a microchannel plate or scintillator according to the present teachings;

FIG. 11B is a schematic illustration of a second exemplary pre-aging mode of a microchannel plate or scintillator according to the present teachings;

FIG. 11C is a schematic illustration of a third exemplary pre-aging mode of a microchannel plate or scintillator according to the present teachings;

FIG. 11D is a schematic illustration of a fourth exemplary pre-aging mode of a microchannel plate or scintillator according to the present teachings;

FIG. 12A is a schematic diagram of a cross-section of a quadrupole mass filter at its exit aperture showing the expected distribution of ions exiting the device under application of a conventional ramped oscillating RF voltage and a conventional ramped DC scan potential difference to the rod electrodes;

FIG. 12B is a schematic diagram of a cross-section of a quadrupole mass filter at its exit aperture, as in FIG. 12A, showing the expected distribution of ions exiting the device with the application of RF and DC voltages, as in FIG. 12A, and supplemented by an additionally applied constant DC potential difference between the X rods and a constant DC potential difference applied between the Y rods; and

FIG. 13 is a schematic diagram of a Mathieu plot showing hypothetical plot points corresponding to ions of different m/z ratios along a hypothetical scan line.

Detailed Description

The following description is presented to enable any person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the described embodiments will be readily apparent to those skilled in the art, and the generic principles herein may be applied to other embodiments. Thus, the present invention is not intended to be limited to the embodiments and examples shown, but is to be accorded the widest scope consistent with the features and principles shown and described. The particular features and advantages of the present invention will become more apparent with reference to the accompanying figures 1-13.

In the description of the invention herein, it is to be understood that words which are presented in the singular form encompass their plural counterparts and words which are presented in the plural form encompass their singular counterparts unless implicitly or explicitly understood or stated otherwise. Furthermore, it should be understood that for any given component or embodiment described herein, any possible candidates or alternatives listed for the component may generally be used alone or in combination with one another, unless implicitly or explicitly understood or stated otherwise. Moreover, it should be appreciated that the figures, as illustrated herein, are not necessarily drawn to scale, wherein only certain elements may be drawn for clarity of the invention. Also, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. Additionally, it should be understood that any list of such candidates or alternatives is merely illustrative, and not limiting, unless implicitly or explicitly understood or stated otherwise.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control. It will be understood that prior to the quantitative terms referred to in the present teachings, an "about" is implied such that minor and insubstantial deviations are within the scope of the present teachings. In this application, the use of the singular includes the plural unless specifically stated otherwise. Furthermore, the use of "comprising", "including", "containing", and "containing" is not intended to be limiting.

As used herein, "a" or "an" may also refer to "at least one" or "one or more". Furthermore, the use of "or" is inclusive such that the phrase "a or B" is true when "a" is true, "B" is true, or both "a" and "B" are true. Furthermore, unless the context requires otherwise, singular terms shall include the plural and plural terms shall include the singular. As used herein, and as commonly used in the field of mass spectrometry, the term "DC" does not specifically refer to or necessarily imply the flow of current, but rather refers to a non-oscillating voltage, which may be constant or variable. Also, as used herein, and as commonly used in the art of mass spectrometry, the term "AC" does not specifically refer to or necessarily imply the presence of alternating current, but rather refers to an oscillating voltage or an oscillating voltage waveform. The term "RF" refers to an oscillating voltage or an oscillating voltage waveform with an oscillating frequency in the radio frequency range.

Fig. 5 is a schematic diagram of a set of quadrupole rods of a mass analyzer. By convention, the four rods are described as a pair of X rods, represented in the figures as rods X1 and X2, and a pair of Y rods, represented in the figures as rods Y1 and Y2. The pair of x-bars define an x-axis that is orthogonal to the long dimension of the bars; likewise, the pair of y-bars define a y-axis that is orthogonal to both the long dimension of the bar and the x-axis. The four bars together define a central longitudinal axis 210 that is parallel to and midway between the four bars. The central longitudinal axis 210 is also denoted as the z-axis, which is orthogonal to both the x-axis and the y-axis.

As in conventional operation, a sweeping Radio Frequency (RF) oscillating voltage RF0, RF pi, and a sweeping Direct Current (DC) voltage DC1+, DC 1-are applied to the rods, with the RF phase applied to the x-rods, which is exactly pi radians out of phase with respect to the phase applied to the y-rods. In other words, the RF potential on the y-bar is reversed relative to the x-bar. Thus, the two phases of RF are denoted in FIG. 5 as RF0 and RF π, respectively. At any moment, the two x-bars have the same potential as each other, as do the two y-bars. The potential on each set of rods can be expressed as having a DC component plus a rapidly oscillating RF component (with a typical frequency of about 1 MHz) relative to a constant potential at the central longitudinal axis 210. The DC potential on the x-bar is positive (relative to the potential on the z-axis), so positive ions feel the restoring force, keeping it close to the z-axis; the potential in the x-direction acts like a well. Conversely, the dc potential on the y-bar is negative (relative to the potential on the z-axis), causing the positive ions to feel a repulsive force, moving them further away from the z-axis; therefore, the potential in the y direction acts like a peak. From the above observations, the DC potential on the x-rod is denoted DC1+ and the DC potential on the y-rod is denoted DC 1-in FIG. 5 and similar figures. The term "DC voltage" as used herein refers to the difference between these two potentials.

Within the quadrupole, ions move inertially along the z-axis from the entrance of the quadrupole to a detector typically placed at the exit of the quadrupole. The ions have trajectories that are separable in the x and y directions within the quadrupole. In the x-direction, the applied RF field carries ions with the smallest mass-to-charge ratio out of the potential well and into the rod. Ions with a sufficiently high mass-to-charge ratio are still trapped in the well and have a stable trajectory in the x-direction; the field applied in the x-direction acts as a high-pass mass filter. In contrast, in the y-direction, only the lightest ions are stabilized by the applied RF field, which overcomes the tendency of the applied DC to pull them into the rod. Thus, the applied field in the y-direction acts as a low-pass quality filter. Ions with stable component trajectories in both x and y pass through the quadrupole to the detector. The DC offset and RF amplitude may be selected so that only ions having a desired range of m/z values are measured. If the RF and DC voltages are fixed, the ions pass through the quadrupole from entrance to exit and exhibit an exit pattern that is a periodic function containing the RF phase. Although the position of the ion departure is based on the dissociable motion, the observed ion oscillation is completely locked to RF. As a result of operating the quadrupole rods in, for example, mass filter mode, the scanning device naturally changes spatial characteristics over time by providing ramped RF and DC voltages, as observed at the exit aperture of the instrument. It is well known that the applied DC voltage can be ramped in coordination with the amplitude of the applied RF voltage waveform, such that the narrow range of m/z ratios gradually increases as the voltage magnitude and amplitude ramp up. Thus, in this context, the applied RF and DC voltages are referred to as scan RF and scan DC voltages, respectively.

In addition, a supplemental resonance excitation Alternating Current (AC) voltage may optionally be applied to the rods to selectively resonantly amplify spatial oscillations of ions having certain m/z values about the axis 210, as discussed further below. The applied AC voltage is an oscillating voltage which differs from the applied RF voltage by its much lower amplitude and slightly lower frequency. The phases of the supplemental AC voltage applied are represented in fig. 9A as AC + and AC-.

Figure 6 schematically depicts a quadrupole rod set 101 and a portion of a temporal and positional imaging ion detector system for a mass spectrometer according to the present teachings. The configuration shown in fig. 6 is very similar to that of fig. 4A. The stream or flux of ions I impinges on the front face 32 of the MCP stack 103 and, in response, electrons e^–Is emitted from the back 34 of the MCP stack. At a bias voltage V supplied by a high voltage power supply 31₁Is pushed from the quadrupole 101 towards the MCP stack. At a bias voltage V₂And V₃The ejected electrons are pushed from the first (upstream) MCP 13a to the last MCP 13c (downstream) of the stack, and then to the front surface 36 of the phosphorescent scintillator 107. Voltage V₃Can be provided to the thin film electrode coating 104 on the front surface 36 of the scintillator 107. In response to electrons striking the front surface 36 of the scintillator 107,photons (h v) are generated within the scintillator and emitted from its back surface 38.

The electronic controller 33, which may be a programmed computer or other integrated circuit programmed by firmware, controls the application of voltages to the MCP and the electrodes 104, and also controls the application of Radio Frequency (RF) and other voltages to the rod electrodes of the quadrupole 101. In a well known manner, the electronic controller 33 may cause the power supply 31 to vary the application of the scan RF and scan Direct Current (DC) voltages during a scan period, which scan voltages are controllably varied during the scan period. Causing ions of progressively increasing or progressively decreasing m/z to be emitted from the quadrupole exit aperture 108. The electronic controller 33 may also cause the power source 31 to apply additional voltage to the rod, as in accordance with the present teachings and as discussed further below. The electronic controller 33 may also control operation of optional actuators coupled to one or both of the scintillator 107 and the MCP stack 103, as discussed further below. In some cases, the application of any additional voltages and the operation of any actuators may be coordinated or synchronized with the application of the scanning RF and DC voltages to the quadrupole rods.

The configuration shown in fig. 6 differs from that shown in fig. 4A in that: (a) by replacing the conventional Ce: YAG phosphor powder, and a scintillator 107; and (b) the MCP stack 103 comprises at least three individual microchannel plates, which are exemplified by plates 13a, 13b and 13c in fig. 6. While both of these modifications are shown in fig. 6, alternative systems are contemplated which include only one of modification (a) or modification (b) as listed above. As another alternative, Ce: the GAGG phosphor may be provided as a sintered powder on the front surface of the substrate 109, similar to the system shown in fig. 4A. If used, the single crystal scintillator has a plate form with a thickness of less than or equal to 1 mm.

The first modification to the detection system described above stems from the observation by the inventors that single crystal scintillator sheets are more resistant to ageing than powders, and that the use of Ce: GAGG as a phosphorescent material yields Ce: YAG has higher gain and simultaneously shows stronger anti-aging capability. If the ratio of Ce: when GAGG is supplied as a sintered powder, the arrangement is as shown in fig. 4A, where Ce: the GAGG powder is coated on a non-phosphorescent substrate. Alternatively, the material can be obtained as a transparent single crystal plate, which has a thickness of about 100 μm. In an alternative configuration where the scintillator (Ce: YAG or Ce: GAGG) comprises a single crystal plate, there may be no substrate, as the scintillator plate 107 itself may be freestanding. With respect to MCP stacks, when three or more microchannel plates are incorporated into such a Z-stack, reduced ionic feedback can slow photocathode aging. The potential gradient is also spread over several plates, so that when three or more microchannel plates are used, each individual plate can experience less electron cluster bombardment.

Various methods of operating a time and position imaging mass spectrometer in order to reduce the rate of aging of MCPs and scintillator packs (both referred to herein as "transducers") are now discussed. According to a first set of such methods, a pair of actuators (not shown) is used to induce motion of at least one of a microchannel plate (MCP) and a scintillator stack relative to a stationary ion beam exiting a quadrupole. These methods cause the ion beam to migrate on, over, near, or around the surface of at least one transducer. Preferably, the transducer of the transducer to be moved is supported on or in a movable carriage (not shown) which is movably connected to the mass spectrometer housing and to the actuator and which is configured for translational movement in a plane parallel to the x and y axes, as defined with reference to the associated quadrupole rods. In operation, the actuators are controlled to move the position of at least one transducer or both transducers simultaneously with respect to the ion beam over a predetermined period of time, e.g., days to weeks. This gradual positional shift through the MCP and/or scintillator plates causes the beam focal zone to continuously impinge on the unaged (or less aged) portion of each transducer surface. The gradual migration of ions or electron beams on the respective transducer surfaces extends the period of time during which the transducer needs to be recalibrated in order to account for aging.

Fig. 7 is a schematic diagram of one example of a pattern of ion or electron beam plate movement across the surface of a transducer during an experimental procedure, wherein the position of the transducer is shifted by coordinated operation of a first actuator (not shown) that translates the transducer parallel to the x-direction and a second actuator (not shown) that translates the transducer parallel to the y-direction. The dashed arrows in fig. 7 depict a hypothetical pattern of motion in which the beam position is first gradually shifted from its initial position at the center 213 of the transducer towards a position near the periphery of the transducer, and then moved around the periphery. Positions 217a, 217b, 217c and 217d represent four such positions at which the light beam is shifted. At each of the illustrated positions, the beam position may not remain stationary; in operation, there may be successive intermediate positions as the beam continuously migrates around the transducer surface. Although the transducer 215 is moved relative to the ion beam during operation of the method, the image of the ion beam on the scintillator plate remains fixed relative to the positions of the quadrupole, the ion beam, and the optical lenses and detectors. Thus, the optics or detector need not be modified.

According to a second set of methods, in accordance with the present teachings, the transducer 215 is held stationary relative to the quadrupole rods in order to cause the ion beam to migrate relative to the paired MCP and scintillator transducers. Instead, the ion beam itself is translated (referred to herein as "steered") by applying supplemental independent DC potentials (denoted DC2a, DC2b, DC2c, and DC2d in fig. 8A) to the quadrupole rods. An unbalanced potential can be controllably applied to either or both of the pairs of rods, with the rods diametrically opposed to each other, to cause the position of the pseudopotential well to move laterally within the quadrupole. In other words, a potential imbalance may span a pair of x-bars and/or a pair of y-bars. Movement of the pseudo-potential well results in a slight translation of the region of maximum ion concentration within the quadrupole away from the central axis of the quadrupole (which remains centered between the rods). This movement of the ion beam causes the center of the ion impact region 211 to migrate away from the center 213 of the transducer.

The ion beam shifting operation may be programmable. For example, if the voltage DC2a applied to rod Y1 is more positive than the voltage DC2c applied to rod Y2, which is diametrically opposite rod Y1, the pseudopotential trap will move away from the central longitudinal axis 210 in the direction of rod Y2. In this case, the center of the positive ion beam within the rod will be similarly displaced. Conversely, if the voltage DC2c were more positive than the voltage DC2a, then the pseudopotential well would be displaced away from the central longitudinal axis 210 in the direction of the rod Y1. Likewise, the difference between the voltage DC2b and the voltage DC2d may be applied in such a way as to displace the pseudopotential trap in the direction of the rod X1 or the rod X2. Fig. 12A is a schematic of a cross-section of a quadrupole mass filter at its exit aperture showing the expected distribution of ions exiting the device under the application of a conventional ramped oscillating RF voltage and a conventional ramped DC scanning potential difference to the rod electrodes, i.e. no additional DC voltages DC2A, DC2b, DC2c and DC2d are applied. It can be seen that in this case the ions exit the mass filter within a tightly confined cloud 402 centered on the central axis of the device. Fig. 12B shows a more expanded distribution of the exiting ions (cloud 404) expected when a steering DC potential difference is applied between rods X1 and X2 and a steering DC potential difference of similar magnitude is applied between rods Y1 and Y2. In this case, the ion density at the central axis decreases, resulting in a reduced velocity of the transducer disposed near the exit aperture.

As an additional benefit, providing these programmable DC steering potentials can be used to achieve controlled position changes during a single m/z scan to provide a unique code (e.g., a code such as a constant offset, a spiral or periodic shift synchronized with an applied RF phase) in the ion trajectory. The controlled application of the DC steering potential can cause beam migration around, near, or across the transducer surface, thereby reducing the rate at which the transducer response degrades at any point on the surface. For example, fig. 8B shows a hypothetical circular beam shift pattern, as may be produced by applying appropriate beam steering potentials as described above. In this example, the beam repeatedly moves along the surface of the microchannel plate 215 from point 218a to point 218b to point 218c and to point 218 d. The beam shift may be stepwise, as shown by the dashed circle in fig. 8B, or may be continuous. Similar electron beam migration will occur around, near or on the surface of the associated scintillator. Other hypothetical beam shift patterns are also possible.

According to another set of methods of the present teachings, a supplemental oscillating Alternating Current (AC) voltage may optionally be applied to the quadrupole rods to selectively resonantly amplify spatial oscillations of ions having certain m/z values about the axis 210. This oscillating AC voltage is distinguished from the oscillating RF voltage by its much lower amplitude and lower frequency. As is well known in the art of mass spectrometry, such resonance excitation imparts additional energy to ions containing the target m/z value, thereby increasing the spatial oscillation amplitude of such excited ions. The amplitude of the AC waveform is selected so that ions having the target m/z value have a greater likelihood of being detected away from (rather than within) the ion focusing region, and so that the target ions are not ejected laterally from the interior of the quadrupole.

The increased amplitude of oscillation of the resonantly excited ions results in a reduced flux of charged particles within the central region 219a of the transducer 215, thereby reducing the overall rate of aging of the transducer within the mass spectrometer. For example, referring to fig. 9B, an ion species having a particular m/z may strike the MCP 215 entirely within the ion strike region 211 without application of a resonance excitation AC voltage. However, when a resonance excitation AC voltage is applied, the impact region may expand to encompass the entire spot-like region 219c, since the fraction of time that ions excited by resonance spend within the ion focus region is reduced. (the ion focusing region is a cylindrical region within the quadrupole concentric with and surrounding the central longitudinal axis 210. the projection of this region onto the MCP 215 is shown as dark stippled region 219A in FIG. 9B.) thus, the total ion flux density (ions-cm) within the stippling 219A is shown^-2-sec^-1) And thus the rate of aging in that region.

The low frequency AC wave, which may be phase synchronized with the RF wave, may be applied on two pairs of rods, with opposite phase on the rods of each pair (i.e., quadrupole excitation), or alternatively, opposite phase on only one pair of rods (i.e., dipole excitation, as shown in fig. 9B). The phases of the applied supplemental AC voltage are represented in fig. 9B as AC0 and AC pi. During operation, the frequency of the AC wave should match the existing frequency or frequencies of the target ions. Both the amplitude and frequency of the wave may be ramped linearly or non-linearly, e.g., exponentially, to achieve the desired ion manipulation. The frequency of the ramp up may include, for example, a series of frequencies that includes a particular long-term frequency of m/z ions.

According to other methods of the present teachings, the transducer elements may be "pre-aged" prior to being placed into service within a quadrupole mass spectrometer device. Pre-ageing of the transducer requires that the surface of the transducer may be selectively exposed to a flux of energetic particles before the transducer is put into use. The pre-aging process takes advantage of the general observation that when the transducer is new, the rate of decrease of the response of the transducer (MCP or scintillator panel) to high energy particle beam strikes is initially fast, but then tapers to zero. When incorporated into an imaging ion detector system, such as one of the systems schematically shown in fig. 1C and 2, the initial rate of decrease in detector response is so great that instrument calibration remains effective for only a few days under normal operating conditions. However, factory burn-in test results (not shown) have shown that the calibration can be spaced several weeks apart after the pre-burn-in process. The described pre-aging process may be employed in place of, or in addition to, any of the beam shifting or resonance excitation methods described above. This pre-aging process may be used in conjunction with an MCP or scintillator assembly of a known time and position imaging mass spectrometer detector system, such as one of the detector systems shown in fig. 1C and 2 or other such systems described in the aforementioned U.S. patent 8,389,929. Alternatively, the described pre-aging process may be used in conjunction with components modified according to either or both of the modifications shown in fig. 6.

Fig. 10A-10B schematically depict a pre-aging process of an MCP or scintillator sheet 215. According to this process, the transducer elements are exposed to a prescribed photon or electron flux (both abbreviated as e) emitted by the LED or electron emitter 301^-) Wherein, in the case of electrons, the flux is initiated by a potential difference provided by a power source electrically coupled to the transducer and the transmitter. This exposure of the newly manufactured transducer to photons/electrons causes the initial response to decrease and be "burned into" the transducer before it is put into use. The exposure to the electron flux is performed for a prescribed period of time and, optionally, according to a prescribed spatial pattern. Since the cross-sectional area of the electron beam is generally smaller than the transduction causing the electrons to impingeThe area of the surface of the transducer, so that the electron beam can be scanned gradually or raster over the surface of the transducer plate by movement of the electron emitter (as schematically indicated by the arrow) or by any other known method, such as beam deflection that is programmatically controlled by a magnetic field.

According to some embodiments, the scan speed of the electron emitter 301 or the current emitted by the emitter (fig. 10A-10B) may be programmatically controlled such that the electron dose density (the number of electrons received per unit area of the transducer) is uniform across the pre-aged transducer surface. According to some other embodiments, the scan speed or emission current may be varied programmatically as the electron beam is scanned across the transducer surface, such that certain predetermined portions of the surface receive greater or lesser degrees of degradation. As an alternative to varying the scan speed or emission current, the electron flux may be partially attenuated in a controlled manner by a mask element 302 disposed between the electron emitter 301 and the transducer 215, as shown in fig. 10B. The mask may be configured to attenuate the photons or electron beam non-uniformly, thereby making the amount of pre-aging (electron dose density) on the transducer non-uniform according to a predetermined spatial pattern. When the transducer is operated in an imaging mass spectrometer, non-uniform pre-ageing allows the transducer surface to be highly sensitive (in a relative sense) to ion current at those locations in the image where the expected ion signal is either less intense or contains highly diagnostic information.

11A-11D illustrate four non-limiting examples of pre-aging modes that may be applied to a transducer 215 to be employed in an imaging mass spectrometer. 11A-11D, the unshaded areas 310 represent a portion of the transducer that is not pre-aged, while the other shaded areas represent pre-aged portions, where the degree of pre-aging is indicated by the darkness of the shading (i.e., more shading indicates more intense pre-aging). The lines defining the various regions are merely intended to geometrically illustrate the various geometric patterns and do not necessarily mean that there are clear boundaries between regions in terms of aging. In practice, the degree of aging may be gradual within a zone or between zones.

The hypothetical pre-aging mode shown in fig. 11A-11C is applicable within a mass spectrometer system in which the transducer remains stationary with respect to the ion beam exiting the mass analyzer, with the center of the transducer disposed along the central longitudinal axis 210 of the extended quadrupole. For example, fig. 11A depicts concentric pre-aging, where the most intense pre-aging is applied around the center 213 of the transducer and the region 313 surrounded by the plurality of concentric annular zones 312, 311, within which the degree of aging gradually decreases from the center outward. This mode ensures that the center of the transducer, which receives the greatest number of ions exiting the mass analyzer (i.e., the ion focusing region), is least susceptible to rapid aging during operation because the center region includes the greatest degree of pre-aging. At the same time, the transducer region displaced from the central region retains greater sensitivity, thus retaining its ability to measure weaker but still diagnostic ion image patterns away from the ion focus region.

FIG. 11B depicts different pre-aging modes that may be produced by directing or aiming an electron beam at each of three separate but partially overlapping regions of the transducer, where each instance of directing or aiming an electron beam causes electrons to strike a corresponding circular region of the transducer, as depicted by the three distinguishable circles in FIG. 11B. In addition to the non-pre-aged region 310, the pattern includes a single center region 316 of maximum pre-aging, three separate and distinct regions 314 of minimum pre-aging, and three other separate and distinct regions 315 of intermediate pre-aging. Similarly, fig. 11C depicts different pre-aging patterns that may be produced by directing or aiming an electron beam at each of four separate but partially overlapping regions of the transducer, where each instance of directing or aiming an electron beam causes electrons to strike a corresponding circular region of the transducer. In addition to the non-pre-aged region 310, the pattern includes a single center region 320 of maximum pre-aging, four separate and distinct regions 317 of minimum pre-aging, four other separate and distinct regions 318 of a first level of intermediate pre-aging, and four other separate and distinct regions 319 of intermediate pre-aging of a second level that is more intense than in the regions 318. In operation, a transducer having the pre-burn-in mode shown in FIG. 11C is preferably aligned such that its mirror symmetry line is aligned in a predetermined manner with the mirror-symmetric (or nearly mirror-symmetric) plane of its associated quadrupole. Such alignment is typically achieved when installing or reinstalling the transducer or transducers including the pre-ageing pattern.

FIG. 11D depicts different pre-aging modes, where the different regions are geometrically arranged as a set of concentric annular rings, the common center of which is the center 213 of the face of the transducer 215. According to this mode, maximum pre-aging occurs within one annular ring 322, and a lesser degree of applied pre-aging occurs within rings 321 both inside and outside of the maximum pre-aged ring 322. Also, there are two non-pre-aged regions, the first of which occurs around the center 213 and the second of which occurs around the perimeter of the transducer 215. The number and width of the annular rings need not be limited to that shown in fig. 11D. This pre-conditioning mode is suitable for use in conjunction with devices in which the ion focusing region is caused to migrate in a circular pattern around the center 213 of the transducer (e.g., fig. 7 and 8B), either by physically manipulating the position of the transducer itself or by electrostatic biasing of the pseudopotential wells within the associated quadrupole rods.

The discussion contained herein is intended to serve as a basic description. The scope of the invention is not to be limited by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and accompanying drawings. Such modifications may fall within the scope of the appended claims. Any patent, patent application publication, or other document referred to herein is incorporated by reference in its entirety, as if fully set forth herein, unless there is any conflict between the incorporated reference and this specification that would prevail in the language of this specification.

Claims (14)

1. An ion detection system for a quadrupole mass analyzer, comprising:

a microchannel plate stack comprising a front face and a rear face, the stack being arranged to receive an ion flux from the exit aperture of the quadrupole rod at the front face and to emit an electron flux in response to the received ion flux at the rear face;

a scintillator having a front surface and a back surface and arranged to receive the electron flux at the front surface and to emit a photon flux at the back surface in response to the received electron flux;

a light imager configured to receive the photon flux;

a power source; and

first, second and third electrodes connected to the power source and disposed on the front, rear and first surfaces, respectively,

wherein the scintillator comprises a single crystal plate of phosphorescent material,

wherein at least one of the scintillator and the microchannel plate stack includes an encoded pre-aging pattern therein, the encoded pre-aging pattern being disposed in a predetermined alignment relative to a set of rod electrodes of the quadrupole rods such that the encoded pre-aging pattern corresponds to an expected ion flux pattern from the quadrupole rods.

2. The ion detection system of claim 1, wherein a thickness of the single crystal plate is less than or equal to 1 millimeter.

3. The ion detection system of claim 1, wherein the phosphorescent material is cerium doped gadolinium aluminum gallium garnet (Ce: GAGG).

4. The ion detection system of claim 1, wherein the phosphorescent material is cerium doped yttrium aluminum garnet (Ce: YAG).

5. The ion detection system of claim 1, further comprising:

an electronic controller is arranged on the base plate,

wherein the power supply is configured to apply separate independent Direct Current (DC) voltages to at least one pair of diametrically opposed rod electrodes of the quadrupole rod in response to control signals received from the electronic controller.

6. The ion detection system of claim 1, further comprising:

an electronic controller is arranged on the base plate,

wherein the power supply is configured to apply, in response to control signals received from the electronic controller, resonant excitation Alternating Current (AC) voltage waveforms of opposite phase on a pair of rods of the quadrupole, the AC voltage waveforms including frequencies matching the oscillation frequencies of the selected ion species within the quadrupole.

7. The ion detection system of claim 1, further comprising:

an electronic controller is arranged on the base plate,

wherein the power supply is configured to apply a resonance excitation alternating current AC voltage waveform comprising a first phase to both of a pair of x-rods of the quadrupole rods in response to a control signal received from the electronic controller,

wherein the power source is configured to apply a resonance excitation alternating current AC voltage waveform comprising a second phase opposite the first phase to both of a pair of y-bars of the quadrupole bar in response to the control signal,

wherein the AC voltage waveform includes a frequency that matches the frequency of oscillation of the selected ion species within the quadrupole.

8. The ion detection system of claim 1, further comprising:

an electronic controller; and

an actuator coupled to at least one of the scintillator and the microchannel plate stack,

wherein the actuator is configured to reposition the at least one of the scintillator and the microchannel plate stack in response to a control signal received from the electronic controller.

9. The ion detection system of claim 1, wherein the microchannel plate stack comprises at least three microchannel plates.

10. A method of performing mass spectrometry comprising:

(a) passing the ion stream through a quadrupole mass analyser comprising a set of rod electrodes;

(b) intercepting an ion flux emitted from an exit aperture of the quadrupole mass analyser at a front of the microchannel plate stack and emitting an electron flux in response to the ion flux intercepted at a rear of the microchannel plate stack;

(c) intercepting the electron flux at a front surface of a scintillator comprising a single crystal plate of phosphorescent material and emitting a photon flux in response to the electron flux intercepted at a rear surface of the scintillator; and

(d) the photon flux is received at a light imager,

wherein the ion flux is intercepted by a front face having an encoded pre-aging pattern therein, the encoded pre-aging pattern being set to a predetermined alignment relative to the set of rod electrodes such that the encoded pre-aging pattern corresponds to an expected ion flux pattern from the quadrupole rod mass analyzer.

11. The method of performing mass spectrometry according to claim 10, wherein intercepting the electron flux at the front surface of a scintillator comprises intercepting an electron flux at the front surface of a single crystal plate of cerium-doped gadolinium aluminum gallium garnet (Ce: GAGG).

12. The method of performing mass spectrometry of claim 10, wherein intercepting the electron flux at a front surface of a scintillator comprises intercepting an electron flux at a front surface of a single crystal plate of cerium-doped yttrium aluminum garnet (Ce: YAG).

13. The method of performing mass spectrometry of claim 10, further comprising:

repositioning at least one of the scintillator and the microchannel plate stack during performance of one or more of steps (a) through (d).

14. The method of performing mass spectrometry of claim 10, further comprising:

laterally repositioning the ion stream within the quadrupole mass analyser during performance of one or more of steps (a) to (d).

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